NDT Advance Access originally published online on October 4, 2005
Nephrology Dialysis Transplantation 2005 20(12):2636-2645; doi:10.1093/ndt/gfi165
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Klotho reduces apoptosis in experimental ischaemic acute renal failure
1 Department of Medicine IV and 2 Department of Blood Purification, Tokyo Women's Medical University, Tokyo, Japan
Correspondence and offprint requests to: Takumi Yoshida, MD, PhD, Department of Blood Purification, Tokyo Women's Medical University, 8–1 Kawada-cho, Shinjuku-city, Tokyo 162-8666, Japan. Email: tyoshida{at}kc.twmu.ac.jp
Background. Klotho is associated with the suppression of several ageing phenotypes. Because high klotho gene expression was detected in the kidney and several studies have found altered expression in animal models, we explored the physiological relevance of klotho expression in the kidney under renal ischemia reperfusion injury (IRI).
Methods. Male Wistar rats were subjected to bilateral renal ischemia or sham operation, followed by reperfusion for 6, 12 or 24 h, or 2 to 10 days. Renal expression of klotho was assessed by real-time PCR or Western blotting. Creatinine levels were determined. Immunohistochemical studies and TUNEL staining were performed. An adenovirus harbouring the mouse klotho gene (ad-kl) was intravenously administered to one group of rats before renal IRI.
Results. Renal klotho mRNA and protein expressions were significantly reduced in IRI rats the first day after ischemia. Pre-treatment with ad-kl resulted in a robust induction of klotho mRNA and protein in the liver but not in the kidney. Ad-kl gene transfer improved serum creatinine and the histological changes. Apoptosis induced by IRI was attenuated following ad-kl administration.
Conclusion. The data suggest klotho to be involved in the pathophysiology of IRI. Downregulation of renal klotho exacerbates ischaemic acute renal failure, and klotho gene induction has therapeutic potential in managing ischaemic renal damage.
Keywords: adenovirus; apoptosis; ischemia reperfusion; klotho
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Sugiura, T. Yoshida, M. Mitobe, S. Yoshida, S. Shiohira, K. Nitta, and K. Tsuchiya Klotho reduces apoptosis in experimental ischaemic acute kidney injury via HSP-70 Nephrol. Dial. Transplant., September 10, 2009; (2009) gfp451v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kuro-o Klotho in chronic kidney disease--What's new? Nephrol. Dial. Transplant., June 1, 2009; 24(6): 1705 - 1708. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Haruna, N. Kashihara, M. Satoh, N. Tomita, T. Namikoshi, T. Sasaki, T. Fujimori, P. Xie, and Y. S. Kanwar Amelioration of progressive renal injury by genetic manipulation of Klotho gene PNAS, February 13, 2007; 104(7): 2331 - 2336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tsuruoka, K. Nishiki, T. Ioka, H. Ando, Y. Saito, M. Kurabayashi, R. Nagai, and A. Fujimura Defect in parathyroid-hormone-induced luminal calcium absorption in connecting tubules of Klotho mice Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2762 - 2767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lewin and K. Olgaard Klotho, an important new factor for the activity of Ca2+ channels, connecting calcium homeostasis, ageing and uraemia Nephrol. Dial. Transplant., July 1, 2006; 21(7): 1770 - 1772. [Full Text] [PDF]
|
|